The SDF-1/CXCR4 chemokine axis in uveal melanoma cell proliferation and migration

Tumour Biol. 2016 Mar;37(3):4175-82. doi: 10.1007/s13277-015-4259-4. Epub 2015 Oct 22.

Abstract

The stromal-cell-derived factor 1 (SDF-1)/chemokine receptor 4 (CXCR4) chemokine axis plays a key role in tumor migration. Here, we analyzed the axis in uveal melanoma (UM) proliferation and migration and investigated the effect of a chemical inhibitor of CXCR4, AMD3100, on UM. We found that CXCR4 was expressed in all five UM cell lines tested as well as the retinal pigment epithelium cell line ARPE-19 cells, while CXCR7 was only detected in OM290 and VUP cell lines. SDF-1 promotes the proliferation and migration of OCM-1 and OCM431 cell lines, while AMD3100 weakens this function. Taken together, our results show that the SDF-1/CXCR4 chemokine axis plays a key role in UM cell proliferation and migration and that AMD3100 can alleviate this function, which may offer a hint for UM treatment.

Keywords: AMD3100; Migration; SDF1/CXCR4; Uveal melanoma.

MeSH terms

  • Benzylamines
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism*
  • Cyclams
  • Gene Expression
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*
  • Uveal Neoplasms / metabolism*
  • Uveal Neoplasms / pathology

Substances

  • Benzylamines
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Cyclams
  • Heterocyclic Compounds
  • Receptors, CXCR4
  • plerixafor

Supplementary concepts

  • Uveal melanoma